Neuron: February 15, 2023 (Volume 111, Issue 4)

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[Cell Symposia: Neurometabolism in health and disease](%2F%2Fwww.cell-symposia.com%2Fneurometabolism-2023%2Fdefault.asp/1/0100018656519a65-3c81695b-3513-4e87-bb15-9061accc6141-000000/O8bjF8xM6kLQIyZuycBxkKt1LamORoDREkUHbjG4bZs=288) In partnership with the Institute of Molecular and Cell Biology, A*STAR Research Entities, Singapore, April 26–28, 2023 | Singapore. Featured articles --------------------------------------------------------------- [Replay and compositional computation](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)01125-4/1/0100018656519a65-3c81695b-3513-4e87-bb15-9061accc6141-000000/x-BeeaBCQsuxw_ZtaRFsf2aeNOjRU6hEePsHgAATkr4=288) Kurth-Nelson et al. [Mouse population genetics phenocopies heterogeneity of human Chd8 haploinsufficiency](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(23)00033-8/1/0100018656519a65-3c81695b-3513-4e87-bb15-9061accc6141-000000/HZcazx8Y3yK2IL_lp-SmfWCWk2L6LSj-nWAKJHGtA6Y=288) Tabbaa et al. [Piezo2 channels expressed by colon-innervating TRPV1-lineage neurons mediate visceral mechanical hypersensitivity](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)01069-8/1/0100018656519a65-3c81695b-3513-4e87-bb15-9061accc6141-000000/CfCDFOvVpWM7Q-3LeXEK7dqYzIfxJ95Vnkt8DRvf6R0=288) Xie et al. [Local memory allocation recruits memory ensembles across brain regions](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)01072-8/1/0100018656519a65-3c81695b-3513-4e87-bb15-9061accc6141-000000/xnQfaZTDYHnjAUG4IofE0HOwlNCJOymw6PSN_TR2NwA=288) Lavi et al. Online now --------------------------------------------------------------- [Glioma epileptiform activity and progression are driven by IGSF3-mediated potassium dysregulation](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(23)00037-5/1/0100018656519a65-3c81695b-3513-4e87-bb15-9061accc6141-000000/P5OsgzX6haeKpV6jfBERFKknz5gKx-29p5tSjrtYvpE=288) Curry et al. [Social deprivation induces astrocytic TRPA1-GABA suppression of hippocampal circuits](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(23)00039-9/1/0100018656519a65-3c81695b-3513-4e87-bb15-9061accc6141-000000/fEGdso8IoRBA81gcScCUKvlXye_JTsvwS5In9X4w9XM=288) Cheng et al. [Neurodegeneration cell per cell](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(23)00064-8/1/0100018656519a65-3c81695b-3513-4e87-bb15-9061accc6141-000000/tdtuwQIYdrQImZdg0E08dpsOXbAWxJh1ZAlWLj_izpM=288) Balusu et al. [Brief synaptic inhibition persistently interrupts firing of fast-spiking interneurons](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(23)00065-X/1/0100018656519a65-3c81695b-3513-4e87-bb15-9061accc6141-000000/RK3Yu9xhTu3kgw3uAuYh-N4LndSCLnPMGfgB5IGC7kU=288) Chamberland et al. Table of Contents Previews --------------------------------------------------------------- [Memory travels through cells backward](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(23)00074-0%3Fdgcid=raven_jbs_etoc_email/1/0100018656519a65-3c81695b-3513-4e87-bb15-9061accc6141-000000/KlYnmycnQ7pCHKq1IoYgiHq0saTTqqfhKpLNSnaimnE=288) José Patricio Casanova, Gisella Vetere Can memory ensembles recruit neurons in connected brain regions? In this issue of Neuron, Lavi et al.1 drove the allocation of memory to selected cells in one area, causing their presynaptic partners to become part of a cross-regional ensemble. [Diverse regional mechanisms drive spinocerebellar ataxia type 1 phenotypes](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(23)00071-5%3Fdgcid=raven_jbs_etoc_email/1/0100018656519a65-3c81695b-3513-4e87-bb15-9061accc6141-000000/7-Q__Ox7FcCJfKfXHnG2h-linbqMcIvCDq94rtTWEeI=288) Alexandra F. Putka, Hayley S. McLoughlin In this issue of Neuron, a pair of studies (Handler et al.1 and Coffin et al.2) elucidate new insights into spinocerebellar ataxia type 1 (SCA1) pathogenesis by genetically assessing mechanistic drivers of regional vulnerability and their relationships to SCA1 phenotypes. [Piezo2 mediates visceral mechanosensation: A new therapeutic target for gut pain?](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(23)00035-1%3Fdgcid=raven_jbs_etoc_email/1/0100018656519a65-3c81695b-3513-4e87-bb15-9061accc6141-000000/EP02awi0cB4j38YdO5EgCZUJ9A7YPxl-LWO1nROd5U0=288) Jing Xu, Aidan McGinnis, Ru-Rong Ji Mechanical distension/stretch in the colon provokes visceral hypersensitivity and pain. In this issue of Neuron, Xie et al. report that mechanosensitive Piezo2 channels, expressed by TRPV1-lineage nociceptors, are involved in visceral mechanical nociception and hypersensitivity. [Dopaminergic signals for improved parental behavior](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(23)00069-7%3Fdgcid=raven_jbs_etoc_email/1/0100018656519a65-3c81695b-3513-4e87-bb15-9061accc6141-000000/WKLn5TZ7Wr_s6KLrtmd4ly-KgDJtazJ5o37vxGtIJCU=288) Zhilei Zhao, Jesse H. Goldberg In this issue of Neuron, Xie et al.1 record and manipulate dopaminergic activity as mice engage in parental care. Dopaminergic prediction error signals previously implicated in food rewards were associated with retrieving isolated pups to the nest, showing that neural mechanisms long associated with reinforcement learning can be repurposed for aspects of parenting. Perspective --------------------------------------------------------------- [Replay and compositional computation](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)01125-4%3Fdgcid=raven_jbs_etoc_email/1/0100018656519a65-3c81695b-3513-4e87-bb15-9061accc6141-000000/tKS8Ka8_R5ugK7ey9FRoOG84W5BXxKUvwZBrtwrH-ZE=288) Zeb Kurth-Nelson, Timothy Behrens, Greg Wayne, Kevin Miller, Lennart Luettgau, Ray Dolan, Yunzhe Liu, Philipp Schwartenbeck Kurth-Nelson et al. propose a new perspective on replay. A replay sequence is a set of entities assembled into a compound. Each entity is bound to its role in the compound, so a sequence can describe a richly articulated structure. Reports --------------------------------------------------------------- [Local memory allocation recruits memory ensembles across brain regions](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)01072-8%3Fdgcid=raven_jbs_etoc_email/1/0100018656519a65-3c81695b-3513-4e87-bb15-9061accc6141-000000/XTjwbvd3wQGdaOYCMYLoDOTaOv2mzTRnPJ5kJmqHfeE=288) Ayal Lavi, Megha Sehgal, Andre F. de Sousa, Donara Ter-Mkrtchyan, Fardad Sisan, Alessandro Luchetti, Anna Okabe, Cameron Bear, Alcino J. Silva Lavi et al. show that ensembles of memory neurons in one brain region recruit presynaptic partners in other regions to participate in memory retrieval. We trace brain-wide connectivity between memory ensembles in mice and discover that they are coordinated by a retrograde mechanism. [Disruption of the ATXN1-CIC complex reveals the role of additional nuclear ATXN1 interactors in spinocerebellar ataxia type 1](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)01070-4%3Fdgcid=raven_jbs_etoc_email/1/0100018656519a65-3c81695b-3513-4e87-bb15-9061accc6141-000000/GgR5meZ9DWijE6rlXSEG6iKR0AhODnPC_sNcZgbf3G0=288) Stephanie L. Coffin, Mark A. Durham, Larissa Nitschke, Eder Xhako, Amanda M. Brown, Jean-Pierre Revelli, Esmeralda Villavicencio Gonzalez, Tao Lin, Hillary P. Handler, Yanwan Dai, Alexander J. Trostle, Ying-Wooi Wan, Zhandong Liu, Roy V. Sillitoe, Harry T. Orr, Huda Y. Zoghbi Open Access Coffin et al. show that global ablation of the ATXN1-CIC interaction normalizes aberrant SCA1 CIC genome-wide binding in mice; however, it does not correct all transcriptional or behavioral changes. They discovered that ATXN1 interacts with multiple factors to drive SCA1, revealing the mechanistic complexity that underlies regional vulnerability in neurodegenerative diseases. Articles --------------------------------------------------------------- [Decreasing mutant ATXN1 nuclear localization improves a spectrum of SCA1-like phenotypes and brain region transcriptomic profiles](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)01071-6%3Fdgcid=raven_jbs_etoc_email/1/0100018656519a65-3c81695b-3513-4e87-bb15-9061accc6141-000000/NoU3e8hfsP_aOcxVrwcnqSx2FfK1IR0eiiSKTZjC98A=288) Hillary P. Handler, Lisa Duvick, Jason S. Mitchell, Marija Cvetanovic, Molly Reighard, Alyssa Soles, Kathleen B. Mather, Orion Rainwater, Shannah Serres, Tessa Nichols-Meade, Stephanie L. Coffin, Yun You, Brian L. Ruis, Brennon O’Callaghan, Christine Henzler, Huda Y. Zoghbi, Harry T. Orr Open Access SCA1, a lethal polyglutamine (polyQ) neurodegenerative disease, displays motor and cognitive impairments. Here, CRISPR-Cas9 was used to mutate the nuclear localization sequence of ATXN1-polyQ in a knockin SCA1 mouse model. The results indicate that ATXN1-polyQ nuclear localization contributes to all SCA1-like phenotypes. However, disease-associated changes in gene expression differ between affected brain regions. [Excessive proteostasis contributes to pathology in fragile X syndrome](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)01035-2%3Fdgcid=raven_jbs_etoc_email/1/0100018656519a65-3c81695b-3513-4e87-bb15-9061accc6141-000000/HpRhVaV00CGQ8kPqOy0V01uogwypwQ2Y9P-TN6uJYYE=288) Susana R. Louros, Sang S. Seo, Beatriz Maio, Cristina Martinez-Gonzalez, Miguel A. Gonzalez-Lozano, Melania Muscas, Nick C. Verity, Jimi C. Wills, Ka Wan Li, Matthew F. Nolan, Emily K. Osterweil Open Access Over-synthesis of proteins in neurons is a core problem in fragile X syndrome, the leading identified monogenic cause of autism. Here, the authors now show over-degradation of proteins is also a contributor to neuropathology. This indicates that the proteostasis cycle is elevated and that reducing protein degradation is a potential new therapeutic strategy. [Piezo2 channels expressed by colon-innervating TRPV1-lineage neurons mediate visceral mechanical hypersensitivity](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)01069-8%3Fdgcid=raven_jbs_etoc_email/1/0100018656519a65-3c81695b-3513-4e87-bb15-9061accc6141-000000/QCSrOWQmQOFiAfOepGqriJGIuT-rocoo_UXG90MKvKA=288) Zili Xie, Jing Feng, Timothy J. Hibberd, Bao Nan Chen, Yonghui Zhao, Kaikai Zang, Xueming Hu, Xingliang Yang, Lvyi Chen, Simon J. Brookes, Nick J. Spencer, Hongzhen Hu Xie et al. show that Piezo2 channels in TRPV1-expressing visceral nociceptors play a major role in visceral pain in mice. Ablation of TRPV1-expressing nociceptors or selective knockout of Piezo2 from TRPV1 lineage neurons reduces colorectal pain under physiological conditions and in mouse models of zymosan-induced IBS and partial colon obstruction. [Mouse population genetics phenocopies heterogeneity of human Chd8 haploinsufficiency](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(23)00033-8%3Fdgcid=raven_jbs_etoc_email/1/0100018656519a65-3c81695b-3513-4e87-bb15-9061accc6141-000000/Ie0MXgvoh41ZQJMgC15OaeKWGcbZdGxikSaLnBP-_II=288) Manal Tabbaa, Allison Knoll, Pat Levitt Open Access Individuals with neurodevelopmental disorders present with wide variability in symptoms, which can be modified by their unique combination of genetic variants. Tabbaa et al. reveal that studying genetic mutations in an ASD-risk gene (Chd8) across many genetically diverse mouse strains recapitulates individual differences in symptom occurrence, manifestation, and severity. [A dopaminergic reward prediction error signal shapes maternal behavior in mice](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)01073-X%3Fdgcid=raven_jbs_etoc_email/1/0100018656519a65-3c81695b-3513-4e87-bb15-9061accc6141-000000/Q5J2BpTQUir8kxwV2Io_dmvE_a24cJh7thy6F45T-1c=288) Yunyao Xie, Longwen Huang, Alberto Corona, Alexa H. Pagliaro, Stephen D. Shea The mechanism by which social contact is perceived as rewarding and shapes future interactions is poorly understood. Xie et al. find that midbrain dopamine neurons signal a social reward prediction error, instructing the emergence of maternal behavior by reinforcement learning and affecting future, but not current, trials. [Flexible sensory-motor mapping rules manifest in correlated variability of stimulus and action codes across the brain](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(22)01032-7%3Fdgcid=raven_jbs_etoc_email/1/0100018656519a65-3c81695b-3513-4e87-bb15-9061accc6141-000000/ukIVF24mwOD9NaS6vbV-qI593Mftc6giyGkubJe4rtA=288) Ruud L. van den Brink, Keno Hagena, Niklas Wilming, Peter R. Murphy, Christian Büchel, Tobias H. Donner Open Access Primates can rapidly switch between different rules that govern the mapping from stimuli to actions. We uncovered a signature of the dynamic reconfiguration of task-specific networks for flexible sensory-motor decisions in the human brain: intrinsic correlations between the population codes for task-relevant stimuli and actions expressed in different brain regions. Corrections --------------------------------------------------------------- [Time coding in rat dorsolateral striatum](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(23)00036-3%3Fdgcid=raven_jbs_etoc_email/1/0100018656519a65-3c81695b-3513-4e87-bb15-9061accc6141-000000/sfdCPU6yBqyev-LPj7W6fWYjXkAJY65WMe8w_R_YC9U=288) Alessandro Toso, Sebastian Reinartz, Francesca Pulecchi, Mathew E. Diamond [Postingestive Modulation of Food Seeking Depends on Vagus-Mediated Dopamine Neuron Activity](%2F%2Fwww.cell.com%2Fneuron%2Ffulltext%2FS0896-6273(23)00075-2%3Fdgcid=raven_jbs_etoc_email/1/0100018656519a65-3c81695b-3513-4e87-bb15-9061accc6141-000000/kWrRu5mYpmfy0cyCZepOFX4YT5-BRyE4XGuTuPeBqpI=288) Ana B. Fernandes, Joaquim Alves da Silva, Joana Almeida, Guohong Cui, Charles R. Gerfen, Rui M. Costa, Albino J. 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